JP2009515892A5 - - Google Patents

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Publication number

JP2009515892A5

JP2009515892A5 JP2008540234A JP2008540234A JP2009515892A5 JP 2009515892 A5 JP2009515892 A5 JP 2009515892A5 JP 2008540234 A JP2008540234 A JP 2008540234A JP 2008540234 A JP2008540234 A JP 2008540234A JP 2009515892 A5 JP2009515892 A5 JP 2009515892A5

Authority

JP

Japan

Prior art keywords

pain

compound

alkyl

aliphatic

hydroxyphenyl

Prior art date

2006-11-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

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• 150000001875 compounds Chemical class 0.000 claims description 305
• 125000000217 alkyl group Chemical group 0.000 claims description 148
• 208000002193 Pain Diseases 0.000 claims description 128
• 239000000203 mixture Substances 0.000 claims description 108
• 125000001931 aliphatic group Chemical group 0.000 claims description 107
• -1 2-hydroxyphenyl Chemical group 0.000 claims description 101
• 230000036407 pain Effects 0.000 claims description 101
• 201000006417 multiple sclerosis Diseases 0.000 claims description 72
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 239000001257 hydrogen Substances 0.000 claims description 60
• 229910052717 sulfur Inorganic materials 0.000 claims description 60
• 239000011734 sodium Substances 0.000 claims description 59
• 239000011780 sodium chloride Substances 0.000 claims description 58
• 229910052760 oxygen Inorganic materials 0.000 claims description 47
• 125000001424 substituent group Chemical group 0.000 claims description 45
• 125000005842 heteroatoms Chemical group 0.000 claims description 43
• UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
• 229910052757 nitrogen Inorganic materials 0.000 claims description 43
• 208000004296 Neuralgia Diseases 0.000 claims description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
• 150000003839 salts Chemical class 0.000 claims description 40
• 229920000728 polyester Polymers 0.000 claims description 35
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbamate Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 33
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 33
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 32
• 201000010099 disease Diseases 0.000 claims description 32
• 125000003118 aryl group Chemical group 0.000 claims description 30
• 125000005843 halogen group Chemical group 0.000 claims description 30
• 125000001072 heteroaryl group Chemical group 0.000 claims description 27
• VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
• 239000001301 oxygen Chemical group 0.000 claims description 24
• MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 24
• NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
• 239000011593 sulfur Chemical group 0.000 claims description 24
• 230000001154 acute Effects 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 20
• 125000003342 alkenyl group Chemical group 0.000 claims description 19
• 125000004429 atoms Chemical group 0.000 claims description 19
• 125000002950 monocyclic group Chemical group 0.000 claims description 18
• 208000008035 Back Pain Diseases 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 206010015037 Epilepsy Diseases 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 14
• 208000005298 Acute Pain Diseases 0.000 claims description 13
• 206010019233 Headache Diseases 0.000 claims description 13
• 125000002619 bicyclic group Chemical group 0.000 claims description 13
• 208000000094 Chronic Pain Diseases 0.000 claims description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 12
• 125000004043 oxo group Chemical group O=* 0.000 claims description 12
• 229910052708 sodium Inorganic materials 0.000 claims description 12
• 208000009935 Visceral Pain Diseases 0.000 claims description 11
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
• 208000006561 Cluster Headache Diseases 0.000 claims description 10
• 206010065390 Inflammatory pain Diseases 0.000 claims description 10
• 206010028836 Neck pain Diseases 0.000 claims description 10
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
• 125000004122 cyclic group Chemical group 0.000 claims description 10
• 125000001153 fluoro group Chemical group F* 0.000 claims description 10
• 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 10
• 201000010874 syndrome Diseases 0.000 claims description 10
• 206010003591 Ataxia Diseases 0.000 claims description 9
• 208000004550 Postoperative Pain Diseases 0.000 claims description 9
• 208000000399 Procedural Pain Diseases 0.000 claims description 9
• RUPAXCPQAAOIPB-UHFFFAOYSA-N Tert-Butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 claims description 9
• 206010044652 Trigeminal neuralgia Diseases 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 208000000003 Breakthrough Pain Diseases 0.000 claims description 8
• 206010007521 Cardiac arrhythmias Diseases 0.000 claims description 8
• 208000004404 Intractable Pain Diseases 0.000 claims description 8
• 208000002551 Irritable Bowel Syndrome Diseases 0.000 claims description 8
• 206010027599 Migraine Diseases 0.000 claims description 8
• 208000008085 Migraine Disorders Diseases 0.000 claims description 8
• 206010029331 Neuropathy peripheral Diseases 0.000 claims description 8
• 206010036376 Post herpetic neuralgia Diseases 0.000 claims description 8
• 230000001684 chronic Effects 0.000 claims description 8
• 201000001119 neuropathy Diseases 0.000 claims description 8
• 229910052698 phosphorus Inorganic materials 0.000 claims description 8
• 206010002855 Anxiety Diseases 0.000 claims description 7
• 206010057666 Anxiety disease Diseases 0.000 claims description 7
• 206010003119 Arrhythmia Diseases 0.000 claims description 7
• 206010058019 Cancer pain Diseases 0.000 claims description 7
• 208000001636 Diabetic Neuropathy Diseases 0.000 claims description 7
• 206010012680 Diabetic neuropathy Diseases 0.000 claims description 7
• 206010022114 Injury Diseases 0.000 claims description 7
• 208000008765 Sciatica Diseases 0.000 claims description 7
• 230000036506 anxiety Effects 0.000 claims description 7
• 150000002431 hydrogen Chemical group 0.000 claims description 7
• 201000008482 osteoarthritis Diseases 0.000 claims description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 206010003246 Arthritis Diseases 0.000 claims description 6
• 206010021639 Incontinence Diseases 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 6
• 206010053643 Neurodegenerative disease Diseases 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 230000004054 inflammatory process Effects 0.000 claims description 6
• 201000009457 movement disease Diseases 0.000 claims description 6
• 230000000955 neuroendocrine Effects 0.000 claims description 6
• 208000006820 Arthralgia Diseases 0.000 claims description 5
• 208000001294 Nociceptive Pain Diseases 0.000 claims description 5
• 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 claims description 5
• 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 claims description 5
• 125000005466 alkylenyl group Chemical group 0.000 claims description 5
• 125000001118 alkylidene group Chemical group 0.000 claims description 5
• 125000002837 carbocyclic group Chemical group 0.000 claims description 5
• 229910052744 lithium Inorganic materials 0.000 claims description 5
• 230000002981 neuropathic Effects 0.000 claims description 5
• 229910052700 potassium Inorganic materials 0.000 claims description 5
• 208000007914 Labor Pain Diseases 0.000 claims description 4
• 230000004913 activation Effects 0.000 claims description 4
• 229910052788 barium Inorganic materials 0.000 claims description 4
• 229910052796 boron Inorganic materials 0.000 claims description 4
• 238000010304 firing Methods 0.000 claims description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 206010003011 Appendicitis Diseases 0.000 claims description 3
• 206010006002 Bone pain Diseases 0.000 claims description 3
• 206010064012 Central pain syndrome Diseases 0.000 claims description 3
• 201000005603 Fabry disease Diseases 0.000 claims description 3
• 208000007514 Herpes Zoster Diseases 0.000 claims description 3
• 206010024229 Leprosy Diseases 0.000 claims description 3
• 206010028391 Musculoskeletal pain Diseases 0.000 claims description 3
• 206010033647 Pancreatitis acute Diseases 0.000 claims description 3
• 208000000450 Pelvic Pain Diseases 0.000 claims description 3
• 206010011302 Peripheral nerve injury Diseases 0.000 claims description 3
• 208000001297 Phlebitis Diseases 0.000 claims description 3
• 206010037175 Psychiatric disease Diseases 0.000 claims description 3
• 206010037596 Pyelonephritis Diseases 0.000 claims description 3
• 206010039073 Rheumatoid arthritis Diseases 0.000 claims description 3
• 206010040037 Sensory neuropathy hereditary Diseases 0.000 claims description 3
• 208000007056 Sickle Cell Anemia Diseases 0.000 claims description 3
• 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims description 3
• 208000008513 Spinal Cord Injury Diseases 0.000 claims description 3
• 206010043255 Tendonitis Diseases 0.000 claims description 3
• 206010043269 Tension headache Diseases 0.000 claims description 3
• 208000008548 Tension-Type Headache Diseases 0.000 claims description 3
• 208000005918 Urinary Bladder Disease Diseases 0.000 claims description 3
• 206010046543 Urinary incontinence Diseases 0.000 claims description 3
• 206010046694 Urogenital disease Diseases 0.000 claims description 3
• 201000003229 acute pancreatitis Diseases 0.000 claims description 3
• 201000008848 bladder disease Diseases 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 238000002512 chemotherapy Methods 0.000 claims description 3
• 201000009541 complex regional pain syndrome Diseases 0.000 claims description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 201000009273 endometriosis Diseases 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 231100000869 headache Toxicity 0.000 claims description 3
• 201000006847 hereditary sensory neuropathy Diseases 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 201000007094 prostatitis Diseases 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 238000001959 radiotherapy Methods 0.000 claims description 3
• 231100000240 steatosis hepatitis Toxicity 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 208000004998 Abdominal Pain Diseases 0.000 claims description 2
• 208000009137 Behcet Syndrome Diseases 0.000 claims description 2
• 201000008335 Behcet's disease Diseases 0.000 claims description 2
• 241000255930 Chironomidae Species 0.000 claims description 2
• 206010015150 Erythema Diseases 0.000 claims description 2
• 206010059204 Labour pain Diseases 0.000 claims description 2
• 208000008930 Low Back Pain Diseases 0.000 claims description 2
• 208000005890 Neuroma Diseases 0.000 claims description 2
• 206010031009 Oral pain Diseases 0.000 claims description 2
• 206010056238 Phantom pain Diseases 0.000 claims description 2
• 206010037779 Radiculopathy Diseases 0.000 claims description 2
• 206010038419 Renal colic Diseases 0.000 claims description 2
• PFNFFQXMRSDOHW-UHFFFAOYSA-N Spermine Natural products NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 claims description 2
• 208000005198 Spinal Stenosis Diseases 0.000 claims description 2
• 208000004371 Toothache Diseases 0.000 claims description 2
• 201000001352 cholecystitis Diseases 0.000 claims description 2
• 231100000321 erythema Toxicity 0.000 claims description 2
• 201000009629 myofascial pain syndrome Diseases 0.000 claims description 2
• 201000009890 sinusitis Diseases 0.000 claims description 2
• 229940063675 spermine Drugs 0.000 claims description 2
• 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims 1
• 206010020853 Hypertonic bladder Diseases 0.000 claims 1
• 206010033425 Pain in extremity Diseases 0.000 claims 1
• 206010037211 Psychomotor hyperactivity Diseases 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 339
• 239000000243 solution Substances 0.000 description 117
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 88
• 238000006243 chemical reaction Methods 0.000 description 58
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
• XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
• YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
• 235000002639 sodium chloride Nutrition 0.000 description 53
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
• 210000004027 cells Anatomy 0.000 description 50
• RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
• 238000004166 bioassay Methods 0.000 description 45
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
• 239000007787 solid Substances 0.000 description 43
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
• 239000012044 organic layer Substances 0.000 description 34
• 230000000694 effects Effects 0.000 description 31
• 239000003814 drug Substances 0.000 description 30
• 230000002829 reduced Effects 0.000 description 30
• AAXRTXWJHOQGMH-OAHLLOKOSA-N ethyl N-[(3R)-1-[7-methyl-2-(6-oxocyclohexa-2,4-dien-1-ylidene)-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OCC)CCN1C(C1=CC=C(C)C=C1N1)=NC1=C1C(=O)C=CC=C1 AAXRTXWJHOQGMH-OAHLLOKOSA-N 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
• 239000011541 reaction mixture Substances 0.000 description 26
• 238000007792 addition Methods 0.000 description 25
• 238000000746 purification Methods 0.000 description 25
• 102000018674 Sodium Channels Human genes 0.000 description 24
• 108010052164 Sodium Channels Proteins 0.000 description 24
• 235000019439 ethyl acetate Nutrition 0.000 description 24
• 230000002401 inhibitory effect Effects 0.000 description 24
• 239000010410 layer Substances 0.000 description 22
• 239000002609 media Substances 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
• 238000010898 silica gel chromatography Methods 0.000 description 21
• 230000000638 stimulation Effects 0.000 description 21
• 150000003840 hydrochlorides Chemical class 0.000 description 20
• 230000004044 response Effects 0.000 description 20
• UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 239000008079 hexane Substances 0.000 description 19
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
• 229940079593 drugs Drugs 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 238000004007 reversed phase HPLC Methods 0.000 description 16
• 239000012299 nitrogen atmosphere Substances 0.000 description 15
• KFTZCNLLRKFMQH-UHFFFAOYSA-M [O-]C(=O)NC1CCNC1 Chemical compound [O-]C(=O)NC1CCNC1 KFTZCNLLRKFMQH-UHFFFAOYSA-M 0.000 description 14
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 14
• 239000002244 precipitate Substances 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• NYKPGDXZKAPBOV-CYBMUJFWSA-N 6-[4-[(3R)-3-aminopyrrolidin-1-yl]-7-methyl-1H-quinazolin-2-ylidene]cyclohexa-2,4-dien-1-one Chemical compound N1C2=CC(C)=CC=C2C(N2C[C@H](N)CC2)=NC1=C1C=CC=CC1=O NYKPGDXZKAPBOV-CYBMUJFWSA-N 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• OJXBCGDDRFYNHN-CQSZACIVSA-N ethyl N-[(3R)-1-[2-(2-fluoro-6-oxocyclohexa-2,4-dien-1-ylidene)-7-methyl-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OCC)CCN1C(C1=CC=C(C)C=C1N1)=NC1=C1C(=O)C=CC=C1F OJXBCGDDRFYNHN-CQSZACIVSA-N 0.000 description 13
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• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
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• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• PNMFDUNMFNUZLN-MRXNPFEDSA-N 2,2-dimethylpropyl N-[(3R)-1-[2-(2-fluoro-6-oxocyclohexa-2,4-dien-1-ylidene)-7-methyl-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound N1C2=CC(C)=CC=C2C(N2C[C@@H](CC2)NC(=O)OCC(C)(C)C)=NC1=C1C(F)=CC=CC1=O PNMFDUNMFNUZLN-MRXNPFEDSA-N 0.000 description 10
• UQVFEKJPGXNHKD-OAHLLOKOSA-N 2-methoxyethyl N-[(3R)-1-[2-(2-fluoro-6-oxocyclohexa-2,4-dien-1-ylidene)-7-methyl-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OCCOC)CCN1C(C1=CC=C(C)C=C1N1)=NC1=C1C(=O)C=CC=C1F UQVFEKJPGXNHKD-OAHLLOKOSA-N 0.000 description 10
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• TWRXJAOTZQYOKJ-UHFFFAOYSA-L MgCl2 Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
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• UFEFTKQQZPGTSD-QGZVFWFLSA-N 2-methylpropyl N-[(3R)-1-[7-methyl-2-(6-oxocyclohexa-2,4-dien-1-ylidene)-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OCC(C)C)CCN1C(C1=CC=C(C)C=C1N1)=NC1=C1C(=O)C=CC=C1 UFEFTKQQZPGTSD-QGZVFWFLSA-N 0.000 description 9
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• ONNGRFCRDXDCDU-QGZVFWFLSA-N 2,2-dimethylpropyl N-[(3R)-1-[7-methyl-2-(6-oxocyclohexa-2,4-dien-1-ylidene)-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound N1C2=CC(C)=CC=C2C(N2C[C@@H](CC2)NC(=O)OCC(C)(C)C)=NC1=C1C=CC=CC1=O ONNGRFCRDXDCDU-QGZVFWFLSA-N 0.000 description 8
• URZQOKSFJRUPIK-MRXNPFEDSA-N 2-methoxyethyl N-[(3R)-1-[7-methyl-2-(6-oxocyclohexa-2,4-dien-1-ylidene)-1H-quinazolin-4-yl]pyrrolidin-3-yl]carbamate Chemical compound C1[C@H](NC(=O)OCCOC)CCN1C(C1=CC=C(C)C=C1N1)=NC1=C1C(=O)C=CC=C1 URZQOKSFJRUPIK-MRXNPFEDSA-N 0.000 description 8
• 210000004556 Brain Anatomy 0.000 description 8
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